Project Summary This revised K01 application is designed to obtain support and time for Dr. Eric Thrailkill (PI) to gain training in translational substance abuse research and experience in conducting human behavioral pharmacology studies with adult daily smokers. This will accomplish the career development goal of expanding the PI?s skills and expertise to include laboratory research with human participants and with human behavioral pharmacology. In this project, the PI will complete an intensive training program in human behavioral pharmacology, translational science, and advanced statistical approaches to data analysis at the University of Vermont under the mentorship of Dr. Stephen Higgins. Dr. Higgins is internationally recognized for his human behavioral pharmacology work with smokers, clinical research on behavior change, and for his mentorship skills. The PI will become skilled in the technical and practical approaches needed to conduct human drug self- administration research with cigarette smokers. The training plan involves development of research and analysis skills in human behavioral pharmacology that will uniquely complement the PI?s background in preclinical research into the basic mechanisms of behavior change and relapse. The PI will maintain a focus on basic learning processes by continuing a training relationship with Dr. Mark Bouton, who has pioneered the study of fundamental behavior change mechanisms in preclinical models. The PI has a unique opportunity to combine the strengths of each mentor into a series of focused studies with adult daily cigarette smokers that will provide the basis for an R01 research project on behavior change mechanisms in smokers. He will apply his newly-developed expertise in human behavioral pharmacology and his background in preclinical relapse models to develop three laboratory models of behavior change and relapse processes at the human level. Each study will use an established, well-validated preparation where individuals under brief smoking abstinence come into a controlled laboratory setting to perform an operant task where they earn brief opportunities to smoke. This method will be used to study underlying processes involved in the reduction and relapse of smoking-reinforced behavior. Studies will examine (1) renewal of an extinguished cigarette-seeking response when the extinction context is changed, (2) resurgence of an extinguished cigarette-seeking response when extinction is introduced for a replacement behavior, and (3) relapse of a nonextinguished -- though suppressed-- cigarette-seeking operant response upon the removal of incentives for a replacement behavior. In addition to providing initial demonstrations of these relapse phenomena with operant responding in human smokers, each study will experimentally evaluate a learning-theory based approach to reducing relapse by enhancing the similarity of the relapse test context and the treatment context. Completing the training and research aims will provide the PI with unique expertise and extensive training in preparation for a career as a leading independent investigator on why treatments work and why individuals relapse.